The CD34 antigen is expressed by committed and uncommitted hematopoietic progenitor cells and is increasingly used to assess stem cell content of peripheral blood progenitor cell (PBPC) collections. Quantitative CD34 expression in PBPC collections has been suggested to correlate with engraftment kinetics of PBPCs infused after myeloablative therapy. We analyzed the engraftment kinetics as a function of CD34 content in 692 patients treated with high-dose chemotherapy (HDC). Patients had PBPCs collected after cyclophosphamide based mobilization chemotherapy with or without recombinant human granulocyte colony-stimulating factor (rhG-CSF) until > or = 2.5 x 10(6) CD34+ cells/kg were harvested. Measurement of the CD34 content of PBPC collections was performed daily by a central reference laboratory using a single technique of CD34 analysis. Forty-five patients required a second mobilization procedure to achieve > or = 2.5 x 10(6) CD34+ cells/kg and 15 patients with less than 2.5 x 10(6) CD34+ cells/kg available for infusion received HDC. A median of 9.94 x 10(6) CD34+ cells/kg (range, 0.5 to 112.6 x 10(6) CD34+ cells/kg) contained in the PBPC collections was subsequently infused into patients after the administration of HDC. Engraftment was rapid with patients requiring a median of 9 days (range, 5 to 38 days) to achieve a neutrophil count of 0.5 x 10(9)/L and a median of 9 days (range, 4 to 53+ days) to achieve a platelet count of > or = 20 x 10(9)/L. A clear dose-response relationship was evident between the number of CD34+ cells per kilogram infused between the number of CD34+ cells per kilogram infused and neutrophil and platelet engraftment kinetics. Factors potentially influencing the engraftment kinetics of neutrophil and platelet recovery were examined using a Cox regression model. The single most powerful mediator of both platelet (P = .0001) and neutrophil (P = .0001) recovery was the CD34 content of the PBPC product. Administration of a post-PBPC infusion myeloid growth factor was also highly correlated with neutrophil recovery (P = .0001). Patients receiving high-dose cyclophosphamide, thiotepa, and carboplatin had more rapid platelet recovery than patients receiving other regimens (P = .006), and patients requiring 2 mobilization procedures versus 1 mobilization procedure to achieve > or = 2.5 x 10(6) CD34+ cells/kg experienced slower platelet recovery (P = .005). Although a minimal threshold CD34 dose could not be defined, > or = 5.0 x 10(6) CD34+ cells/kg appears to be optimal for ensuring rapid neutrophil and platelet recovery.
Although previous studies have suggested an increased relative risk of BWS and AS after ART, our findings suggest that the absolute risk of imprinting disorders in children conceived by ART is small (<1%). Precise risk estimates of risk are difficult to define because of the rarity of the conditions and incomplete response rates to the questionnaire and clinical examination invitations. Hence further investigations are indicated to (i) refine the absolute and relative risks of imprinting disorders after ART and (ii) ensure that changes in ART protocols are not associated with increased frequencies of epigenetic changes and imprinting disorders in children born after ART.
The purpose of this study was to determine the effectiveness of second mobilization strategies in patients who yielded < 2.5 x 10(6) CD34+ PBSC/kg after initial mobilization. Repeat mobilization attempts were made with chemotherapy and G-CSF (n = 61) or G-CSF alone (n = 58) in patients who failed initial mobilization with chemotherapy and G-CSF (n = 92) or G-CSF alone (n = 27). A median of 0.27 x 10(6) CD34+ cells/kg per apheresis was collected after the second mobilization, compared with 0.16 with initial harvests (p = 0.0001). Forty-eight percent achieved a target CD34+ cell dose > or = 2.5 x 10(6)/kg when harvests from the first and second mobilizations were combined. Fifteen of 17 patients (88%) with > or = 1.5 x 10(6) CD34+ cells/kg harvested after first mobilization had > or = 2.5 x 10(6) CD34+ cells/kg collected when first and second harvests were combined, as compared with 42 of 102 (41%) achieving < 1.5 x 10(6) CD34+ cells/kg with first PBSC harvests (p = 0.0001). Second mobilizations with chemotherapy and G-CSF or G-CSF alone resulted in similar CD34+ cell yields. Toxicities of second mobilizations were comparable with those of first mobilizations. Seventy-nine patients (66%) received high-dose chemotherapy with PBSC support, with recovery of neutrophils and platelets in a median of 11 and 15 days, respectively. Transplant-related mortality was 4%, and event-free survival at 2 years was 0.34. It was concluded that second mobilization attempts in patients who fail to achieve > or = 2.5 x 10(6) CD34+ cells/kg on initial mobilization were successful in 48% of patients. G-CSF alone was as effective as chemotherapy plus G-CSF in mobilizing CD34+ cells and was associated with less morbidity.
It is estimated that approximately 1% of the newborn population of the British Isles are conceived following assisted reproduction technologies such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI). While the long term outcome of IVF children is mostly reassuring, some concerns remain. Specifically, recent studies have suggested a possible association between assisted conception and clinical conditions of genetic origin known as genomic imprinting defects. This has arisen from several different studies observing an excess of assisted conceptions among the rare clinical disorders of Beckwith–Wiedemann syndrome (BWS) and Angelman syndrome (AS). The numbers of such patients described in the studies to date are small but indicate a clear need for large‐scale investigations to clarify the link between genomic imprinting defects and assisted conception as well as to establish the exact biological basis of any such link. In view of the strong public interest in this area of medicine, it behoves all professionals working in reproductive medicine and associated areas to be aware of these emerging data and be in a position to discuss them in as informed and responsible a manner with patients, as current data limitations permit.
Summary:there was more rapid recovery of platelets in patients receiving the higher CD34 + cell doses. 4 Some patients receiving Ͻ2-2.5 × 10 6 CD34 + cells/kg have greatly Engraftment kinetics after high-dose chemotherapy (HDC) were evaluated in patients receiving autologous delayed platelet recovery as compared to patients receiving a higher cell dose. 3,5-7 peripheral blood stem cell (PBSC) infusions with a low CD34 ؉ cell content. Forty-eight patients were infusedIt has also been suggested that there are factors other than CD34 + cell dose involved in hematologic recovery with Ͻ2.5 ؋ 10 6 CD34 ؉ cells/kg; 36 because of poor harvests and 12 because they electively received only a after HDC and PBSC infusion. For example, in a series of 225 patients with multiple myeloma receiving HDC, the fraction of their harvested cells. A median of 2.12 ؋ 10 6 CD34 ؉ cells/kg (range, 1.17-2.48) were infused followinfusion of 2.0 × 10 6 CD34 + cells/kg resulted in rapid engraftment in patients who had received Ͻ6 months of ing one of seven different HDC regimens. All patients achieved absolute neutrophil counts у 0.5 ؋ 10 9 /l at a therapy with melphalan, but Ͼ5 × 10 6 CD34 + cells/kg were required for rapid platelet recovery in patients who had median of day 11 (range, 9-16). Forty-seven patients achieved platelet counts у 20 ؋ 10 9 /l at a median of day received Ͼ12 months of melphalan. 8 Target CD34 + cell doses of 2.5 or 5.0 × 10 6 /kg are easily 14 (range, 8-250). Nine of 47 (19%) had platelet recovery after day 21, 4/47 (9%) after day 100 and one died achievable in the majority of patients. [3][4][5] In a relatively small fraction of heavily pretreated patients, however, these on day 240 without platelet recovery. Twenty-six patients (54%) died of progressive disease in 51-762 cell doses are not obtainable. 3-5 Furthermore, sequential or tandem administration of HDC followed by the infusion of days; 22 (46%) are alive at a median of 450 days (range, 94-1844), 17 (35%) of whom are surviving disease-free a fraction of harvested PBSC can result in the administration of relatively low CD34 + cell numbers after each at a median of 494 days (range, 55-1263). No patient died as a direct consequence of low blood cell counts.treatment. The purpose of this analysis was to evaluate the These data demonstrate that PBSC products containing 1.17-2.48 ؋ 10 6 CD34 ؉ cells/kg resulted in relatively engraftment kinetics in 48 patients with malignancy given HDC followed by PBSC containing Ͻ2.5 × 10 6 CD34 + prompt neutrophil recovery in all patients but approximately 10% had delayed platelet recovery. cells/kg. Keywords: engraftment; low CD34 ϩ cells Patients and methodsThe CD34 + cell content of peripheral blood stem cells Patient selection (PBSC) has been shown to be an accurate and proven predictor of engraftment kinetics, especially of platelets, folRecords were reviewed of 2079 nonleukemia patients lowing high-dose chemotherapy (HDC). 1-5 Infusion of treated with HDC and PBSC infusion between March 1991 PBSC containing у5 × 10 6 /k...
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